原创力文档myc and miz-1 have coordinate genomic functions including targeting hox genes in human embryonic stem cellsmyc和miz-1协调基因组功能包括针对hox基因在人类胚胎干细胞.pdfVIP
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myc and miz-1 have coordinate genomic functions including targeting hox genes in human embryonic stem cellsmyc和miz-1协调基因组功能包括针对hox基因在人类胚胎干细胞
Varlakhanova et al. Epigenetics Chromatin 2011, 4:20
/content/4/1/20
RESEARCH Open Access
Myc and Miz-1 have coordinate genomic
functions including targeting Hox genes
in human embryonic stem cells
1,2,3 1,2,3 2 2,4 1,2,3*
Natalia Varlakhanova , Rebecca Cotterman , Keith Bradnam , Ian Korf and Paul S Knoepfler
Abstract
Background: A proposed role for Myc in maintaining mouse embryonic stem (ES) cell pluripotency is
transcriptional repression of key differentiation-promoting genes, but detail of the mechanism has remained an
important open topic.
Results: To test the hypothesis that the zinc finger protein Miz-1 plays a central role, in the present work we
conducted chromatin immunoprecipitation/microarray (ChIP-chip) analysis of Myc and Miz-1 in human ES cells,
finding homeobox (Hox) genes as the most significant functional class of Miz-1 direct targets. Miz-1 differentiation-
associated target genes specifically lack acetylated lysine 9 and trimethylated lysine 4 of histone H3 (AcH3K9 and
H3K4me3) 9 histone marks, consistent with a repressed transcriptional state. Almost 30% of Miz-1 targets are also
bound by Myc and these cobound genes are mostly factors that promote differentiation including Hox genes.
Knockdown of Myc increased expression of differentiation genes directly bound by Myc and Miz-1, while a subset
of the same genes is downregulated by Miz-1 loss-of-function. Myc and Miz-1 proteins interact with each other
and associate with several corepressor factors in ES cells, suggesting a mechanism of repression of differentiation
genes.
Conclusions: Taken together our data indicate that Miz-1 and Myc maintain human ES cell pluripotency by
coordinately suppressing differen
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